Consent

Objectives

To determine whether participants with poorly controlled asthma have improved asthma control and lung capacity when prescribed a soy isoflavone supplement versus a placebo.

Background

The prevalence of asthma is determined by multiple environmental and genetic factors, and over the last several decades, both the prevalence and severity of asthma have increased. Specific causes remain unknown, but diet is one of the environmental factors associated with increased prevalence and severity.

Previous studies had shown that those who consume soy isoflavones have better lung function compared to those who do not. The study focused on two particular iosflavones, genistein and daidzein, based on the strong preclinical and epidemiological data that supported the prediction of beneficial dietary effects for asthma patients. At the cellular level, genistein exerts antioxidant effects that are equal to or greater than those of vitamin C. Prior to the clinical trial, recent in vitro results showed that genistein inhibits synthesis of human peripheral blood eosinophil cysteinyl leukotrienes via inhibition of 5-lipoxygenase. Synthesis of the eosinophil cysteinyl leukotrienes is a key pathways that may contribute to asthma severity.

Subjects

Eligible participants were over the age of 12, of either gender, and were non-smokers for 6 months or longer with a less than 10 pack-year smoking history. The SOYA trial had 193 participants randomized into the placebo and soy isoflavone arms for a total of 386 participants. 179 participants in the placebo arm and 166 participants in the soy isoflavone arm completed the trial, which was defined as having an FEV1 measurement at 24 weeks.

Participants were included if they had been diagnosed by a physician with asthma, were currently prescribed daily controller asthma medication, or had a FEV1 equal or greater than 50% predicted pre-bronchodilator and/or at least 12% increase in FEV1 15-3 minutes after inhaling 2-4 puffs of albuterol or positive methacholine challenge (20% fall in FEV1 at less than 8 mg/mL) with either parameter available from the previous two years. Participants with poor asthma control were included if they met at least one of the following: a score of 1.5 or greater on the Juniper Asthma Control Questionnaire, use of beta-agonist for asthma symptoms two or more times per week, nocturnal awakening with asthma symptoms more than once per week, and/or two or more episodes of asthma symptoms in the past 12 months with each requiring at least one of the following: emergency department visit, unscheduled physician visit, prednisone course, and/or hospitalization.

Participants were excluded from the trial for potential non-adherence or allergy to treatment, not meeting FEV inclusion criteria, use of concurrent and/or prior (<6 weeks) trial medications, and other major chronic illnesses that may interfere with participation based on the judgement of the study physician. Changes in diet, a body weight of less than 77 pounds (35kg), a high intake of soy or soy-enriched foods 1 or more times per week, recent upper respiratory infections (<2 weeks) and asthma exacerbations (<6 weeks) were additional exclusionary criteria.

Design

SOYA was a phase 4 interventional clinical trial. The study was multicenter, randomized, and double blind. Parallel assignment treatment arms were structured to determine the efficacy of soy supplementation and diet modification on asthma control.

The primary outcome measured was the mean change in forced expiratory volume in the first second (FEV1), at the 24 week visit. Secondary outcomes were asthma symptoms, episodes of poor asthma control, Asthma Control Test score, and systemic and airway biomarkers of inflammation.

Participants were randomly assigned in a 1:1 allocation ratio to receive either the soy isoflavone supplement or matching placebo twice daily for six months. Participants were instructed to keep daily diaries recording the following: morning peak expiratory flow, medication use, and asthma symptoms. Participants reported taking at least 1 dose of the study treatment on more than 90% of follow-up days. Clinical assessments and procedures were completed every 4 weeks for a total of 24 weeks. The Block Food Frequency Questionnaire and Soy Foods Screener were administered at visits 2 and 9. Data from daily diaries and pill counts were used to evaluate adherence to the treatment protocol. Each participant’s overall diet and dietary soy intake were analyzed at baseline and at 24 weeks to assess stability of diet and nutrient intake during the study.

Conclusions

Participants who received the soy isoflavone supplement exhibited an increase in mean plasma genistein levels; however, no clinically significant improvement was observed in the primary end point of FEV1 at 24 weeks post-randomization between participants treated with soy isoflavone supplement and placebo.

JAMA. 2015 May 26;313(20):2033-43

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